Nishimoto, Yoshinori

写真a

Affiliation

School of Medicine, Department of Internal Medicine (Neurology) (Shinanomachi)

Position

Senior Assistant Professor (Non-tenured)/Assistant Professor (Non-tenured)
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Profile Summary 【 Display / hide 】

  • Clinical research
    Keio University School of Medicine, Ethics Committee Approval Number：20221155
    「Clinical studies to elucidate the molecular mechanisms associated with the pathogenesis of amyotrophic lateral sclerosis (ALS) and to identify eff ective drug targets」(UMIN000051823)(ver 2.3/updated on July 6, 2023)

    Frontiers Editor Board member (Frontiers in Molecular Neuroscience journal)

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Career 【 Display / hide 】

  • 2022.04
    -
    Present

    慶應義塾大学 医学部, 神経内科, 専任講師

  • 2020.04
    -
    2022.03

    慶應義塾大学医学部, 神経内科, 助教

  • 2018.04
    -
    2020.03

    慶應義塾大学医学部, 百寿総合研究センター, 特任助教

  • 2016.10
    -
    2018.03

    東京都済生会中央病院, 神経内科, 医員

  • 2016.08
    -
    2018.03

    慶應義塾大学 医学部, 生理学教室, 助教

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Academic Background 【 Display / hide 】

  • 2003.04

    Keio University Graduate School of Medicine, Internal Medicine, Neurology

    Graduate School, Graduated, Doctoral course

  • 1997.04

    Keio University, Shool of Medicine

    University, Graduated

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Academic Degrees 【 Display / hide 】

  • MD, Keio University, Coursework, 2003.03

  • PhD, Keio University, Coursework, 2008.10

    Determination of editors at the novel A-to-I editing positions.

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Licenses and Qualifications 【 Display / hide 】

  • 日本国 医師免許

  • 日本内科学会認定 総合内科専門医

  • 日本内科学会認定 認定内科医

  • 日本内科学会認定 指導医

  • 日本神経学会認定 神経内科専門医

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Matters concerning Career Achievements 【 Display / hide 】

  • 2023.01
    -
    Present

    臨床研究 承認番号：20221155 「筋萎縮性側索硬化症(ALS)の病態に関連する分子メカニズムの解明と効果的薬剤標的を同定するための臨床研究」

    　View Details

    臨床研究
    慶應義塾大学医学部・病院　倫理委員会　承認番号：20221155
    「筋萎縮性側索硬化症(ALS)の病態に関連する分子メカニズムの解明と効果的薬剤標的を同定するための臨床研究」(第1.2版/2023年1月12日承認)

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Research Areas 【 Display / hide 】

  • Life Science / Neurology

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Research Keywords 【 Display / hide 】

  • 筋萎縮性側索硬化症 (ALS)

  • 神経変性疾患

  • 神経分子生物学

  • 神経再生医学

  • RNA/ノンコーディングRNA

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Research Themes 【 Display / hide 】

  • Establishment of full-care system for the patients with amyotrophic lateral sclerosis (ALS), 

    2003.04
    -
    Present

  • 筋萎縮性側索硬化症(ALS)の核酸医薬による分子標的療法の開発, 

    2010.07
    -
    Present

  • 次世代シークエンス技術を活用した認知症の遺伝的リスク算出法の確立, 

    2018.04
    -
    Present

  • 認知症のオンライン診療データを活用した自動病態評価技術の開発, 

    2020.07
    -
    Present

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Books 【 Display / hide 】

  • 脳神経内科ゴールデンハンドブック (ALSほか運動ニューロン疾患 分担執筆)

    西本 祥仁, 南江堂, 2020.06

    Scope: 運動ニューロン疾患及び類縁疾患

  • Chapter I 高齢者社会の現状とフレイル・ロコモ・サルコペニアの意義 3．百寿とはどのような方か？

    西本祥仁, 新井康通, クリニコ出版, 2019.11

  • Drosophila Oogenesis: Methods and Protocols

    Shibata S, Murota Y, Nishimoto Y, Yoshimura M, Nagai T, Okano H, Siomi MC., 2015

    Scope: Immuno-Electron Microscopy and Electron Microscopic In Situ Hybridization for Visualizing piRNA Biogenesis Bodies in Drosophila Ovaries.

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Papers 【 Display / hide 】

  • Multiple lines of evidence for disruption of nuclear lamina and nucleoporins in FUS amyotrophic lateral sclerosis

    Okada K., Ito D., Morimoto S., Kato C., Oguma Y., Warita H., Suzuki N., Aoki M., Kuramoto J., Kobayashi R., Shinozaki M., Ikawa M., Nakahara J., Takahashi S., Nishimoto Y., Shibata S., Okano H.

    Brain 147 ( 11 ) 3933 - 3948 2024.11

    ISSN  00068950

    　View Summary

    Advanced pathological and genetic approaches have revealed that mutations in fused in sarcoma/translated in liposarcoma (FUS/TLS), which is pivotal for DNA repair, alternative splicing, translation and RNA transport, cause familial amyotrophic lateral sclerosis (ALS). The generation of suitable animal models for ALS is essential for understanding its pathogenesis and developing therapies. Therefore, we used CRISPR-Cas9 to generate FUS-ALS mutation in the non-classical nuclear localization signal (NLS), H517D (mouse position: H509D) and genome-edited mice. FusWT/H509D mice showed progressive motor impairment (accelerating rotarod and DigiGait system) with age, which was associated with the loss of motor neurons and disruption of the nuclear lamina and nucleoporins and DNA damage in spinal cord motor neurons. We confirmed the validity of our model by showing that nuclear lamina and nucleoporin disruption were observed in lower motor neurons differentiated from patient-derived human induced pluripotent stem cells (hiPSC-LMNs) with FUS-H517D and in the post-mortem spinal cord of patients with ALS. RNA sequence analysis revealed that most nuclear lamina and nucleoporin-linking genes were significantly decreased in FUS-H517D hiPSC-LMNs. This evidence suggests that disruption of the nuclear lamina and nucleoporins is crucial for ALS pathomechanisms. Combined with patient-derived hiPSC-LMNs and autopsy samples, this mouse model might provide a more reliable understanding of ALS pathogenesis and might aid in the development of therapeutic strategies.

  • Depressive symptoms and carotid arteriosclerosis in very old people aged 85 years and older: A cross-sectional study by the Kawasaki Aging and Wellbeing Project.

    Ryo Shikimoto, Takashi Sasaki, Yukiko Abe, Yoshinori Nishimoto, Takumi Hirata, Masaru Mimura, Yasumichi Arai

    Psychiatry and Clinical Neurosciences 78 ( 3 ) 209 - 211 2024

    Accepted

  • Determinants of polydoctoring among multimorbid older adults; a cross-sectional study in an urban area of Japan

    Takayuki Ando, Takashi Sasaki, Yukiko Abe, Yoshinori Nishimoto, Takumi Hirata, Junji Haruta, Yasumichi Arai

    Journal of General and Family Medicine 25 ( 6 ) 376 - 383 2024

    Accepted

    　View Summary

    Background: Multimorbidity increases with age, leading to various adverse outcomes, including higher mortality, care dependency, hospitalizations, and healthcare costs. Polydoctoring, managing a patient with multimorbidity by multiple healthcare providers, can be a risk of fragmented care and increased healthcare expenditures. This study aims to identify patient-related factors contributing to polydoctoring in older adults with multimorbidity. Methods: This study is a cross-sectional study using baseline data from the Kawasaki Aging and Wellbeing Project. Participants were residents of Kawasaki City aged 85–89 years, without disability in basic activities of daily living, and being able to visit study site. The regularly visited facilities (RVF) index was employed to quantify polydoctoring. Polydoctoring was defined as having two or more RVFs. Poisson regression analysis was conducted to assess the association between polydoctoring and patient demographics, including types of chronic conditions and socioeconomic factors. Results: A total of, 968 participants with multimorbidity were analyzed. Increased RVF was significantly associated with eye diseases (rate ratio [RR] 1.27, 95% confidence interval [CI] 1.12–1.44), osteoporosis (RR 1.22, 95% CI 1.08–1.38), prostate diseases (RR 1.22, 95% CI 1.07–1.40), and osteoarthritis (RR 1.16, 95% CI 1.05–1.27). No significant correlation was found with educational status or financial hardship. Conclusion: The study indicated that certain chronic conditions are linked to increased polydoctoring among multimorbid older adults in Japan. However, most of those conditions are considered to be within a scope of family medicine/general practice. Training general practitioners to manage these conditions could reduce healthcare costs and the treatment burden, indicating a direction for future healthcare policy and medical education.

  • Association of polydoctoring and mortality among persons over 85 years with multimorbidity: a prospective cohort study in Japan

    Ando T., Sasaki T., Abe Y., Nishimoto Y., Hirata T., Tajima T., Oguma Y., Haruta J., Arai Y.

    BJGP Open 8 ( 3 )  2024

    　View Summary

    Background: Polydoctoring can increase the risk of care fragmentation among patients with multimorbidity, but its impact on health outcomes remains unclear. Aim: To determine the effects of polydoctoring, as measured by the regularly visited facilities (RVF) indicator, on patient outcomes among older individuals with multimorbidity. Design & setting: Data from the ongoing prospective cohort study, Kawasaki Aging and Wellbeing Project (KAWP), was utilised in this study. Among the 1026 KAWP participants aged 85–89 years, those with two or more chronic conditions were enrolled in this study. Method: Care fragmentation and polydoctoring was evaluated using the RVF, which is a new indicator that measures the number of medical facilities consistently involved in a patient’s care. Based on RVF, mortality was analysed using the Cox proportional hazards model, with adjustments for age, sex, frailty, and number of comorbidities. Results: A significant reduction in mortality rates was observed in participants with an RVF of ≥3 and 2–4 comorbidities (hazard ratio [HR] 0.43, 95% confidence interval [CI] = 0.18 to 0.99, P value = 0.048). However, no significant difference in mortality based on RVF was observed for those with ≥5 comorbidities. Notably, individuals with ≥5 comorbidities and an RVF of 0 had a significantly higher HR for death (HR 2.68, 95% CI = 1.05 to 6.84, P value = 0.039). Conclusion: In older patients with multimorbidity, polydoctoring may reduce mortality in patients with ≤4 coexisting conditions, but it does not significantly impact mortality in those with ≥5 conditions. These findings provide insights for healthcare decision making in managing older patients with multimorbidity.

  • Impact of Amyloid and Tau PET on Changes in Diagnosis and Patient Management

    Sho Shimohama, Toshiki Tezuka, Takahata Keisuke, Shogyoku Bun, Hajime Tabuchi, Morinobu Seki, Yuki Momota, Natsumi Suzuki, Ayaka Morimoto, Yu Iwabuchi, Masahito Kubota, Yasuharu Yamamoto, Yasunori Sano, Ryo Shikimoto, Kei Funaki, Yu Mimura, Yoshinori Nishimoto, Ryo Ueda, Masahiro Jinzaki, Jin Nakahara, Masaru Mimura, Daisuke Ito

    Neurology (Neurology)  100 ( 3 ) e264 - E274 2023

    Accepted,  ISSN  00283878

    　View Summary

    Background and Objectives: Previous studies have evaluated the diagnostic effect of amyloid PET in selected research cohorts. However, these studies did not assess the clinical impact of the combination of amyloid and tau PETs. Our objective was to evaluate the association of the combination of 2 PETs with changes in diagnosis, treatment, and management in a memory clinic cohort.Methods: All participants underwent amyloid [18F]florbetaben PET and tau PET using [18F]PI-2620 or [18F]Florzolotau, which are potentially useful for the diagnosis of non-Alzheimer disease (AD) tauopathies. Dementia specialists determined a pre- and post-PET diagnosis that existed in both a clinical syndrome (cognitive normal [CN], mild cognitive impairment [MCI], and dementia) and suspected etiology, with a confidence level. In addition, the dementia specialists determined patient treatment in terms of ancillary investigations and management. Results: Among 126 registered participants, 84.9% completed the study procedures and were included in the analysis (CN [n = 40], MCI [n = 25], AD [n = 20], and non-AD dementia [n = 22]). The etiologic diagnosis changed in 25.0% in the CN, 68.0% in the MCI, and 23.8% with dementia. Overall changes in management between pre- and post-PET occurred in 5.0% of CN, 52.0% of MCI, and 38.1% of dementia. Logistic regression analysis revealed that tau PET has stronger associations with change management than amyloid PET in all participants and dementia groups. Discussion: The combination of amyloid and tau PETs was associated with changes in management and diagnosis of MCI and dementia, and the second-generation tau PET has a strong impact on the changes in diagnosis and management in memory clinics. Classification of Evidence: This study provides Class I evidence that the combination of amyloid and tau PETs was associated with changes in management and diagnosis of MCI and dementia.

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Papers, etc., Registered in KOARA 【 Display / hide 】

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Reviews, Commentaries, etc. 【 Display / hide 】

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

  • 2024年度「ALS基金」研究奨励金「ALS傷害運動ニューロンにおけるトランスポゾン制御異常の病態解明」

    2024

    日本ALS協会, 2024年度「ALS基金」研究奨励金, Principal investigator

  • 武田科学振興財団 医学系研究助成 (精神・神経・脳領域) 「核内非翻訳RNA制御によるALS患者由来運動ニューロン変性抑制の試み」

    2022

    Principal investigator

  • 文部科学省 科学研究費補助金　基盤研究(C)　「ALSゲノム編集マウスを用いたGC/UGリッチRNA配列での病態考察と治療法開発」

    2021.04
    -
    2025.03

    Research grant, Principal investigator

  • KGRI (Keio University Global Research Institute)スタートアップ研究補助 (KGRI startup award) 「オンライン診療を用いた認知症診療の有効性、安全性評価」

    2020.07
    -
    2022.03

    Research grant, Principal investigator

  • 日本学術振興会 海外特別研究員 「Investigating the regulatory function of the exosome complex in RNA metabolism a nd motor neuron disease」

    2014
    -
    2015

    Principal investigator

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Works 【 Display / hide 】

  • 朝日学生新聞連載コラム「からだの教室 -知識の玉手箱-」

    西本 祥仁

    朝日学生新聞 毎週金曜日 全26回, 

    2014.04
    -
    2014.09
    , 

    Other

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Awards 【 Display / hide 】

  • Education Award (Medixpost)

    2024.11, 「筋萎縮性側索硬化症(ALS)の患者を診断してからの第一歩」

    Type of Award： Award from publisher, newspaper, foundation, etc.

  • Neurogenetics Editor’s Pick 2021 (Frontiers in Neurology)

    2021.08

    Type of Award： Honored in official journal of a scientific society, scientific journal

  • KGRI (Keio University Global Research Institute) Startup Award

    2020.06, Keio University Global Research Institute, 「オンライン診療を用いた認知症診療の有効性、安全性評価」

    Type of Award： Keio commendation etc.

  • Selected key poster (Harvard Stem Cell Institute Retreat)

    2016.05, 11th Annual Harvard Stem Cell Institute Malkin Retreat 2016, 「Altered tRNA metabolism links RNA Exosome deficiency with motor neuron disease」

  • Physician's Recognition Award

    2015.08, American Medical Association, 「Pediatric Advanced Care Team Rounds」

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Courses Taught 【 Display / hide 】

  • LECTURE SERIES, INTERNAL MEDICINE (NEUROLOGY)

    2024

  • LECTURE SERIES, INTERNAL MEDICINE (NEUROLOGY)

    2023

  • LECTURE SERIES, INTERNAL MEDICINE (NEUROLOGY)

    2022

  • LECTURE SERIES, INTERNAL MEDICINE (NEUROLOGY)

    2021

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